miR-30a attenuates drug sensitivity to 5-FU by modulating cell proliferation possibly by downregulating cyclin E2 in oral squamous cell carcinoma

Kenta Kawahara; Masashi Nagata; Ryoji Yoshida; Akiyuki Hirosue; Takuya Tanaka; Yuichiro Matsuoka; Hidetaka Arita; Hikaru Nakashima; Junki Sakata; Keisuke Yamana; Sho Kawaguchi; Shunsuke Gohara; Yuka Nagao; Masatoshi Hirayama; Nozomu Takahashi; Mayumi Hirayama; Hideki Nakayama

Biochemistry and Biophysics Reports (Dec 2021)

miR-30a attenuates drug sensitivity to 5-FU by modulating cell proliferation possibly by downregulating cyclin E2 in oral squamous cell carcinoma

Kenta Kawahara,
Masashi Nagata,
Ryoji Yoshida,
Akiyuki Hirosue,
Takuya Tanaka,
Yuichiro Matsuoka,
Hidetaka Arita,
Hikaru Nakashima,
Junki Sakata,
Keisuke Yamana,
Sho Kawaguchi,
Shunsuke Gohara,
Yuka Nagao,
Masatoshi Hirayama,
Nozomu Takahashi,
Mayumi Hirayama,
Hideki Nakayama

Affiliations

Kenta Kawahara: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Masashi Nagata: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Ryoji Yoshida: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Akiyuki Hirosue: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Takuya Tanaka: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan; Department of Dentistry and Oral Surgery, Amakusa Central General Hospital, Amakusa 863-0033, Japan
Yuichiro Matsuoka: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Hidetaka Arita: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Hikaru Nakashima: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan; Department of Oral & Maxillofacial Surgery, Kyushu Central Hospital, Fukuoka 815-8588, Japan
Junki Sakata: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Keisuke Yamana: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Sho Kawaguchi: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Shunsuke Gohara: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Yuka Nagao: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Masatoshi Hirayama: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Nozomu Takahashi: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Mayumi Hirayama: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan
Hideki Nakayama: Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan; Corresponding author.

Journal volume & issue: Vol. 28
p. 101114

Abstract

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We aimed to determine the functional role of the miRNA, which affects drug sensitivity to 5-FU in oral squamous cell carcinoma (OSCC), using two types of 5-FU-resistant and parental OSCC cell lines. MiRNA microarray data showed that miR-30a was significantly upregulated in two resistant cell lines. Therefore, we investigated the effects and molecular mechanism of miR-30a on 5-FU sensitivity. Stable overexpression of miR-30a in parental OSCC cells decreased cell proliferation and attenuated drug sensitivity to 5-FU. Cell cycle analysis indicated that miR-30a overexpression increased the proportion of G1 phase cells and decreased the proportion of S phase cells. MiR-30a knockdown using siRNA reversed the effects of miR-30a overexpression. DNA microarray analysis using miR-30a-overexpressing cell lines and a TargetScan database search showed that cyclin E2 (CCNE2) is a target of miR-30a. A luciferase reporter assay confirmed that a miR-30a mimic interacted with the specific binding site in the 3' UTR of CCNE2. CCNE2 knockdown with siRNA in OSCC cells yielded decreased drug sensitivity to 5-FU, similar to miR-30a overexpressing cells. These findings suggest that miR-30a in OSCC may be a novel biomarker of 5-FU-resistant tumors, as well as a therapeutic target for combating resistance.

Published in Biochemistry and Biophysics Reports

ISSN: 2405-5808 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General); Science: Chemistry: Organic chemistry: Biochemistry
Website: http://www.journals.elsevier.com/biochemistry-and-biophysics-reports/

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